Extra- and intracellular amino acids in the hippocampus during development of hepatic encephalopathy

Hamberger, Anders; Nyström, Britta

doi:10.1007/bf00973033

Cited by 103 publications

(63 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, despite findings of increased cerebrospinal fluid and extracellular brain levels of glutamate (6)(7)(8)(9)32), as well as increased brain tissue and cerebrospinal fluid levels of the excitotoxin quinolinic acid in both clinical and experimental hepatic encephalopathy (26,27), we could not demonstrate excitotoxic brain damage in experimental acute hepatic encephalopathy using 45CAC12 autoradiography. The latter technique has been shown to be a sensitive tool to demonstrate cerebral calcium accumulation, in pathological conditions associated with excitotoxicity (19)(20)(21)28).…”

Section: Discussioncontrasting

confidence: 56%

“…The latter technique has been shown to be a sensitive tool to demonstrate cerebral calcium accumulation, in pathological conditions associated with excitotoxicity (19)(20)(21)28). Furthermore, increases of extracellular brain glutamate, during cerebral ischemia (3.5-8 fold) (29) and hypoglycemia (2.5 fold) (30), conditions considered to be associated with glutamate-related neurototoxicity, are similar to those found during acute liver failure (6)(7)(8). In addition, hippocampus and striatum were chosen because these brain regions are known to contain a large number of glutamate receptors (33).…”

Section: Discussionmentioning

confidence: 79%

“…Experimental acute hepatic encephalopathy and acute hyperammonemia appear to be associated with increased extracellular brain concentrations of glutamate (6)(7)(8)(9). In addition, increased glutamate concentrations are also found in cerebrospinal fluid of patients with hepatic encephalopathy (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Strategy for reliable prenatal detection of normal male carriers of the fragile X syndrome

et al. 1994

View full text Add to dashboard Cite

In experimental hepatic encephalopathy and hyperammonemia, extracellular levels of glutamate are increased in hippocampus and cerebral cortex. It has been suggested that overstimulation of glutamate receptors causes a pathological entry of calcium into neurons via receptor-operated (NMDA-and AMPA-type) or voltage-dependent calcium channels leading to calcium overload and cell death. Neurodegeneration as a result of exposure to excitotoxins, including glutamate, can be localized and quantified using 45CAC12 autoradiography. This approach was used to study cerebral calcium accumulation in rabbits with acute liver failure and acute hyperammonemia. Acute liver failure was induced in 6 rabbits, acute hyperammonemia in 4 rabbits; 4 control rabbits received sodium-potassium-acetate. At the start of the experiment 500 IxCi 45CAC12 was given intravenously. After development of severe encephalopathy, the animals were killed by decapitation. All rabbits with acute liver failure or acute hyperammonemia developed severe encephalopathy, after 13.2±1.7 and 19.3±0.5 hours respectively (mean±SEM). Plasma ammonia levels were 425±46 and 883±21 ~mol/1, respectively (p<0.05). Control rabbits maintained normal plasma ammonia levels (13±5 txmol/1), demonstrated normal behaviour throughout the study and were sacrificed after 16 hours. 45Ca2+-autoradiograms of 40 ttm brain sections were analyzed semiquantitatively using relative optical density and computerized image analysis. As compared to background levels 45Ca was not increased in hippocampus or any other brain area of rabbits with severe encephalopathy from acute liver failure or acute hyperammonemia. This suggests that, despite increased extracellular brain glutamate levels in these conditions, glutamate neurotoxicity was not important for the development of encephalopathy in these rabbits.

show abstract

Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Strategy for reliable prenatal detection of normal male carriers of the fragile X syndrome

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Extracellular and vesicular glutamate represent only a small fraction of total brain glutamate. 68,69 Conceivably, lithium at levels generally associated with maintenance therapy may exert an inducing effect on Glu through stimulation of neuronal and glial metabolism, neurogenesis in the hippocampus as well as gliogenesis in the hippocampus and possibly elsewhere in the brain. Along these lines, we have recently reported that glutamate levels in the dorsolateral prefrontal cortex in major depression increase with clinical improvement.…”

Section: Discussionmentioning

confidence: 99%

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

et al. 2008

View full text Add to dashboard Cite

While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T 1 Hmagnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients > controls) and laterality (left hippocampus > right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.

show abstract

“…In comparison with glutamic acid, the concentrations of glutamine in plasma and cerebrospinal fluid are 1-3 orders of magnitude higher (14,16), whereas those of GABA are at least a magnitude lower or negligible (14,17). However, the concentrations of all three in brain are between 5 and 50 mM (14,16 (19).…”

Section: Discussionmentioning

confidence: 99%

L-glutamic acid, a neurotrophic factor for maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Koelle¹,

Sanville²,

Thampi³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In continuation of previous studies, the intraarterial fusion of L-glUtamiC acid for 24 hr was found to oppose the decrease in acetylcholinesterase and butyrylcholinesterase in the superior cervical ganglion of the cat that otherwise occurs 48 hr after preganglionic denervation. The combination of glutamic acid and raminobutyric acid, in concentrations that were inactive individually, likewise produced the same neurotrophic effect. Inactive in this respect were glycine plus L-glutamine, pyroglutamic acid, y-aminobutyric acid, and L-aspartic acid. The possible mechanisms and implications of these rmdings are discussed.Previous studies in this series have demonstrated that the 24-hr intracarotid infusion of an aqueous extract of cat brain, spinal cord, and sciatic nerves in cats opposes (1, 2) the fall in the acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) and butyrylcholinesterase (BtChoEase; acylcholine acylhydrolase, EC 3.1.1.8) contents of the superior cervical ganglia (SCG) that otherwise occurs 48 hr after section of the cervical sympathetic trunks (1, 3, 4). The neurotrophic factor responsible for this effect was found to be a heat-stable compound of low molecular weight (Mr, <1000) and probably a peptide (5). It was postulated (6) that the neurotrophic factor might act by regulating the conversion of the G1 to the G4 and A12 molecular aggregates of the enzymes (7). Following a report (8) that glycyl-L-glutamine (Gly-Gln) exhibited such an effect in cultured embryonic rat and chicken skeletal muscle, and because this compound met the criteria indicated above, it was tested in the cat in vivo preparation. Results indicated that a metabolite of Gly-Gln is an active neurotrophic factor. Of three possible metabolites tested, glycine and L-glutamine were found to be inactive but glycyl-L-glutamic acid (GlyGlu) was significantly active (9).In the present study, we report the results of testing similarly some possible metabolites of Gly-Glu and related compounds. L-Glutamic acid was found to be an active neurotrophic factor when infused in the concentration range of 10 to 300 ,uM. The combination of 1 ,uM glutamic acid and 100 AM y-aminobutyric acid (GABA) in concentrations that were inactive individually was also effective. Combinations of glycine plus L-glutamine were inactive, as were pyroglutamic acid, GABA, and L-aspartic acid. METHODSAnesthetic and surgical procedures and the methods for homogenization of ganglia and for determination of their AcChoEase, BtChoEase, and protein contents and for calculation of statistical significance of mean differences were identical with those reported (1). Under sodium pentobarbital anesthesia (35 mg/kg intraperitoneally) 1 cm was resected from both cervical sympathetic trunks; the wound was sutured and Combiotic (penicillin/dihydrostreptomycin, 0.5 ml intramuscularly; Pfizer, New York) was given. The following day, cats were again anesthetized, ifrecovered, and atropinized (1.0 mg/kg, intraperitoneal4y); artificial respiration was admin...

show abstract

Extra- and intracellular amino acids in the hippocampus during development of hepatic encephalopathy

Cited by 103 publications

References 20 publications

Strategy for reliable prenatal detection of normal male carriers of the fragile X syndrome

Strategy for reliable prenatal detection of normal male carriers of the fragile X syndrome

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

L-glutamic acid, a neurotrophic factor for maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat.

Contact Info

Product

Resources

About